Dental caries arises as a result of major ecological imbalances on the tooth surface. Clearly, these imbalances arise from environmental stresses which include, but are not limited to, acid production from sugars and heavy metals. Microorganisms can adapt to stress through up-regulation of several genes and production of gene products. This adaptation may enhance the virulence of oral microorganisms. The availability of substrates to overcome the stress of an acidogenic environment, e.g. salivary peptides, can help to reduce the need for adaptation by oral microorganisms, and at the same time reduce the prevalence of dental caries. Heavy metals, particularly lead, constitute one of the major environmental stressors, particularly in children. Lead is pervasive and can affect tooth formation, salivary function, and perhaps microorganisms. The Program Project offered here proposes to explore, in a closely coordinated fashion, the interaction of the environment, stressors, and dental caries. Three projects are offered: 1) Salivary Arginine/Lysine/Peptides and Caries Experience (Drs. Tabak, Billings, and Moss); 2) Adaptation to Environmental Stresses and Dental Caries (Drs. Marquis, Burne, and Quivey); 3) and Influence of Heavy Metals (Lead) on Salivary Gland Function and Dental Caries (Drs. Bowen, Melvin, and Watson). In addition, there is an Administrative Core (Dr. Bowen) and a Biostatistical Core (Dr. Raubertas). All of the investigators have extensive experience in theft fields. The Program Project will interface with existing caries research, and training grants within the Department of Dental Research. An Advisory Committee has been formed, which includes four external consultants (Drs. Joseph Ferretti, Mark Herzberg, Irwin Mandel, and Jason Tanzer) who reviewed the current proposals and will advise on research progress, evaluation, and new approaches. Dr. Paul La Celle, Senior Associate Dean, University of Rochester, is special consultant to the proposed director. Dr. Thomas Clarkson, Director of Environmental Health Sciences Center, University of Rochester, will serve as consultant. Information arising from the Program Project will be disseminated through publications and presentations at local seminars and national meetings.